title: Quantification of excision repair cross-complementing group 1 and survival in p16-negative squamous cell head and neck cancers.
abstract: OBJECTIVE
  Multimodality treatment of squamous cell carcinoma of the head and neck (SCCHN) often involves radiotherapy and cisplatin-based therapy. Elevated activity of DNA repair mechanisms, such as the nucleotide excision repair (NER) pathway, of which ERCC1 is a rate-limiting element, are associated with cisplatin and possibly RT resistance. We have determined excision repair cross-complementing group 1 (ERCC1) expression in human papillomavirus (HPV)-negative SCCHN treated with surgery [± adjuvant radiotherapy/chemoradiation (CRT)].
  
  
  METHODS
  We assessed ERCC1 protein expression in archival tumors using immunofluorescence staining and automatic quantitative analysis (AQUA) with three antibodies to ERCC1 (8F1, FL297, and HPA029773). Analysis with Classification and Regression Tree (CART) methods ascertained the cutoff points between high/low ERCC1 expression. Multivariable analysis adjusted for age, T, and N stage. Kaplan-Meier curves determined median survival. ERCC1 expression at initial tumor presentation and in recurrent disease were compared. Performance characteristics of antibodies were assessed.
  
  
  RESULTS
  ERCC1 low/high groups were defined on the basis of AQUA analysis with 8F1/2009, FL297, and HPA029773. Among patients treated with surgery plus adjuvant radiotherapy/CRT, longer median survival was observed in ERCC1-low versus ERCC1-high tumors (64 vs. 29 months; P = 0.02; HPA029773). Data obtained with HPA029773 indicated no survival difference among patients treated only with surgery. Recurrent cancers had lower ERCC1 AQUA scores than tumors from initial presentation. Extensive characterization indicated optimal specificity and performance by the HPA029773 antibody.
  
  
  CONCLUSIONS
  Using AQUA, with the specific ERCC1 antibody HPA029773, we found a statistical difference in survival among high/low-ERCC1 tumors from patients treated with surgery and adjuvant radiotherapy.
authors.affiliation: Authors' Affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Ranee
authors.initials: R
authors.lastname: Mehra
authors.forename: Fang
authors.initials: F
authors.lastname: Zhu
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Yang
authors.forename: Kathy Q
authors.initials: KQ
authors.lastname: Cai
authors.forename: Joellen
authors.initials: J
authors.lastname: Weaver
authors.forename: Mahendra K
authors.initials: MK
authors.lastname: Singh
authors.forename: Anna S
authors.initials: AS
authors.lastname: Nikonova
authors.forename: Erica A
authors.initials: EA
authors.lastname: Golemis
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Flieder
authors.forename: Harry S
authors.initials: HS
authors.lastname: Cooper
authors.forename: Miriam
authors.initials: M
authors.lastname: Lango
authors.forename: John A
authors.initials: JA
authors.lastname: Ridge
authors.forename: Barbara
authors.initials: B
authors.lastname: Burtness
mesh_terms: D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D003131:Combined Modality Therapy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D006801:Humans; D047468:Immunoprecipitation; D053208:Kaplan-Meier Estimate; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000517:prevention & control; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases